International Journal of Mycobacteriology 1 (2012) 165– 169 Available at www.sciencedirect.com journal homepage: www.elsevier.com/locate/IJMYCO Review Epidemiology of cervico-facial pediatric lymphadenitis as a result of nontuberculous mycobacteria Enrico Tortoli * Emerging Bacterial Pathogens Unit, San Gabriele Building, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milano, Italy ARTICLE INFO ABSTRACT Article history: Cervical lymphadenitis as a result of nontuberculous mycobacteria, otherwise known as Received 13 October 2012 scrofula, is a disease occurring almost exclusively in immunocompetent young children. Accepted 29 October 2012 The most frequent mycobacterial species responsible is Mycobacterium avium, but a large Available online 20 November 2012 number of other species may also be involved. The epidemiology of such disease is revised here, and the impact of different species as causative agents of adenitis is also discussed. Keywords: Ó 2012 Asian-African Society for Mycobacteriology. All rights reserved. Cervical lymphadenitis Nontuberculous mycobacteria Epidemiology M. avium M. haemophilum M. malmoense Contents Introduction .................................................................................... 166 Clinical notes . ................................................................................ 166 Epidemiology . ................................................................................ 166 Mycobacterium scrofulaceum. .................................................................. 166 MAC...................................................................................... 166 Mycobacterium simiae complex. ........................................................... 167 Mycobacterium haemophilum .................................................................. 167 Other slowly growing species . .................................................................. 167 Rapidly growing species . .................................................................. 167 Discussion .................................................................................... 167 References .................................................................................... 168 * Tel.: +39 3292422105; fax +39 0226435183. E-mail address: [email protected]. 2212-5531/$ - see front matter Ó 2012 Asian-African Society for Mycobacteriology. All rights reserved. http://dx.doi.org/10.1016/j.ijmyco.2012.10.008 166 International Journal of Mycobacteriology 1 (2012) 165– 169 Introduction mercialization of sensitins, despite the regret of some pedia- tricians, confirms their limited value. Scrofula is a mycobacterial disease of the lymph nodes of the The most resolutive intervention is nowadays considered head and neck well known during ancient times; in the Mid- the complete excision of the affected lymph nodes before dle Ages, it was also called the ‘‘king’s evil,’’ as it was believed the suppuration occurrence; the healing is obtained in a large the disease could be healed by the touch of royalty. Both proportion of cases, but recurrences are not exceptional. tuberculous and nontuberculous mycobacteria (NTM) can be Other less usual possibilities include no intervention, antimi- responsible for cervical lymphadenitis. crobial therapy alone, fine needle aspiration and incision fol- The cases of scrofula, which were very common in the lowed by drainage or curettage. past, are, at least in the great majority, imputable to Mycobac- terium tuberculosis and Mycobacterium bovis; in the xx century Epidemiology this kind of disease has steadily decreased and is now very rare in developed countries, but, starting with the 1950s, an Differently from NTMs isolated from pulmonary specimens – increasing number of cases as a result of NTMs have been re- which only in a limited number of cases are clinically signif- ported [1]. icant – the mycobacteria isolated from lymph nodes can Scrofula is typically a disease of childhood, but rare cases never be considered contaminants or colonizers. The number in adults have also been documented. The focus of this review of NTM species responsible for cervical lymphadenopathy is is on the epidemiology of cervical lymphadenitis of otherwise very high, and so far some of them have only been isolated healthy children, with the exclusion therefore of cases affect- from lymph nodal biopsies. ing immunocompromised patients. Mycobacterium scrofulaceum Clinical notes M. scrofulaceum is one of the oldest of the NTM species; it was The disease typically affects immunocompetent children, described in 1956 by Prissick and Masson in a report concern- most prevalent in those between the ages of 1 and 5 years ing ten cases of a new variant of scrofula presenting with a old. It is hypothesized that NTMs present in the environment nontuberculous etiology [2]. Major emphasis is placed in this are ingested and enter the body through lesions in the oral paper on the slow growth and the yellow pigmentation of the mucosa (e.g. in concomitance with dental eruption), or by newly detected mycobacterium. The vagueness of such fea- way of the lymphatic vessels that drain the mouth and phar- tures, compatible with many mycobacterial species, were, ynx. The lymph nodes most commonly affected include the along with the name ‘‘scrofulaceum’’, destined to influence jugulodigastric, submandibular, parotid/pre-auricular, sub- the identification of mycobacteria isolated from adenitis over mental and posterior triangle. In most of the cases, the pa- a long period of time. tient is asymptomatic; less frequent symptoms can include Beginning in the 1970s, Wolinsky [3] reported an ‘‘abrupt a slight fever and malaise. The first manifestation is a non- change in the predominant etiologic agent from M. scrofulaceum tender, indolent, mostly unilateral swelling (1–6 cm) which to Mycobacterium avium complex’’ (MAC). Both the prevalent subsequently enlarges and, in consequence of the necrosis involvement of MAC and the paucity of cases due to of the central part of the granulomatous lesions, liquefies M. scrofulaceum remain unchanged nowadays. becoming fluctuant. The skin becomes often violaceous as a consequence of the inflammatory reaction, and frequently MAC the necrotic collection fistulizes. In a limited number of cases, spontaneous healing occurs The first case of cervical lymphadenitis due to M. avium was by fibrosis and calcification; regression is quite rare. reported in 1959 [4]; in subsequent years, when the taxonomic The initial stages of the disease are frequently interpreted status of MAC was still far from being defined and related as an incidental upper respiratory tract infection and antibi- organisms were referred to as ‘‘Battey group’’, the first case otics are prescribed which, however, prove to be ineffective. series were published [5,6]. Starting in the 1980s, Mycobacte- Differential diagnosis with tuberculous or pyogenic adenitis rium intracellulare was also beginning to be reported among is needed, and the isolation of the agent in a culture is of par- the agents of lymphadenitis. It remains, however, undistin- amount importance. For this purpose, the use of a liquid med- guished from M. avium of which it is considered a variant ia is advisable to reduce the burden of cases with positive [7]. The introduction of serotyping made for the first time pos- acid-fast microscopy which fails to grow if cultured on solid sible a reliable distinction between M. avium and M. intracellu- media only. lare, but, at the same time, produced the ambiguity of the The skin test based on intradermal inoculation of sensi- association of such species with M. scrofulaceum, in the M. avi- tins, tuberculin analogs specific from the most common um-intracellulare-scrofulaceum (MAIS) group [8]. With the com- NTMs, has been used for many years to diagnose, in absence mercialization of the nucleic acid probes, the definitive of a culture, NTM lymphadenitis; the diagnostic accuracy of distinction of M. avium and M. intracellulare became within such tests is at least questionable because of the high level the reach of diagnostic laboratories. of cross-reactions between the different antigens and with Recently, a large-scale study [9] did not detect any case due the tuberculin skin test itself. The discontinuation of com- to M. intracellulare in a group of children with adenitis. The International Journal of Mycobacteriology 1 (2012) 165– 169 167 same study demonstrated furthermore that all the strains of Mycobacterium mantenii [36], Mycobacterium palustre [26], Myco- M. avium investigated belonged to the subspecies hominissuis, bacterium tusciae [37] and Mycobacterium asiaticum [38]. In most with M. avium subsp. avium being totally absent. cases, such strains were included among the ones character- In recent years, MAC has been enriched by several new ized for the description of the new species. Mycobacterium species; of them, only Mycobacterium colombiense has been re- bohemicum, an uncommon mycobacterium indeed, has been ported responsible for lymphadenitis [10,11]. reported responsible for a relatively high number of cases of scrofula [39]. Mycobacterium simiae complex Mycobacterium gordonae and the members of the Mycobacte- rium terrae complex are only exceptionally responsible for dis- M. simiae, grown for the first time from a monkey, is a multi- ease in humans. Such characteristic is apparently confirmed drug-resistant species frequently isolated in several geo- for adenitis since for the first species, there is only one report graphic areas,